Previous studies have demonstrated that the F isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase(6PF2K/Fru-2,6-BPase) is transcriptionally regulated by growth factors. The aim of this study was to investigate the importance of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway in the regulation of 6PF2K/Fru-2,6-BPase gene expression. We have completed studies using chemical inhibitors and expression vectors for the proteins involved in this signalling cascade. Treatment of cells with LY 294002, an inhibitor of PI 3-kinase, blocked the epidermal growth factor (EGF)-dependent stimulation of 6PF2K/Fru-2,6-BPase gene transcription. Transient transfection of a constitutively active PI 3-kinase was sufficient to activate transcription from the F-type 6PF2K/Fru-2,6-BPase promoter. In contrast, co-transfection with a dominant-negative form of PI 3-kinase completely abrogated the stimulation by EGF, and down-regulated the basal promoter activity. In an attempt to determine downstream proteins that lie between PI 3-kinase and 6PF2K/Fru-2,6-BPase gene expression, the overexpression of a constitutively active form of protein kinase B (PKB) was sufficient to activate 6PF2K/Fru-2,6-BPase gene expression, even in the presence of either a dominant-negative form of PI 3-kinase or LY 294002. The over-expression of p70/p85 ribosomal S6 kinase or the treatment with its inhibitor rapamycin did not affect 6PF2K/Fru-2,6-BPase transcription. We conclude that PI 3-kinase is necessary for the transcriptional activity of F-type 6PF2K/Fru-2,6-BPase, and that PKB is a downstream effector of PI 3-kinase directly involved in the regulation of 6PF2K/Fru-2,6-BPase gene expression.
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July 2000
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Research Article|
June 26 2000
Activation of phosphatidylinositol 3-kinase is required for transcriptional activity of F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: assessment of the role of protein kinase B and p70 S6 kinase
Silvia FERNÁNDEZ DE MATTOS;
Silvia FERNÁNDEZ DE MATTOS
1Departament de Bioquímica i Biologia Molecular, Div. IV, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, E08028 Barcelona, Catalunya, Spain
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Elisabet DE LOS PINOS;
Elisabet DE LOS PINOS
1Departament de Bioquímica i Biologia Molecular, Div. IV, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, E08028 Barcelona, Catalunya, Spain
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Manel JOAQUIN;
Manel JOAQUIN
1Departament de Bioquímica i Biologia Molecular, Div. IV, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, E08028 Barcelona, Catalunya, Spain
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Albert TAULER
Albert TAULER
1
1To whom correspondence should be addressed (e-mail tauler@;farmacia.far.ub.es).
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Publisher: Portland Press Ltd
Received:
October 18 1999
Revision Received:
March 10 2000
Accepted:
April 26 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 349 (1): 59–65.
Article history
Received:
October 18 1999
Revision Received:
March 10 2000
Accepted:
April 26 2000
Citation
Silvia FERNÁNDEZ DE MATTOS, Elisabet DE LOS PINOS, Manel JOAQUIN, Albert TAULER; Activation of phosphatidylinositol 3-kinase is required for transcriptional activity of F-type 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: assessment of the role of protein kinase B and p70 S6 kinase. Biochem J 1 July 2000; 349 (1): 59–65. doi: https://doi.org/10.1042/bj3490059
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